Which drugs are FDA indicated for Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) in known or suspected Still’s disease, including Systemic Juvenile Idiopathic Arthritis (sJIA)?

FDA Indications for HLH/MAS in Still's Disease and sJIA

Based on the FDA label evidence, none of the drugs mentioned (anakinra, tocilizumab, ruxolitinib/baricitinib, or etoposide) are specifically FDA-indicated for HLH/MAS in the context of Still's disease or sJIA. 1

Analysis of Available Evidence

The FDA label for tocilizumab (Actemra) provides detailed information about its approved indications and dosing:

• Tocilizumab is FDA-approved for:
  • Rheumatoid Arthritis (RA)
  • Giant Cell Arteritis (GCA)
  • Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD)
  • Polyarticular Juvenile Idiopathic Arthritis (pJIA)
  • Systemic Juvenile Idiopathic Arthritis (sJIA)
  • Cytokine Release Syndrome (CRS)
  • COVID-19

While tocilizumab is approved for sJIA, the FDA label does not specifically mention approval for HLH/MAS complications in sJIA or Still's disease 1. The label provides detailed dosing information for sJIA but does not include specific dosing or indications for HLH/MAS management.

Clinical Implications

This is an important distinction for clinicians to understand:

• Although these medications (particularly IL-1 and IL-6 inhibitors like anakinra and tocilizumab) may be used off-label in clinical practice for HLH/MAS in Still's disease/sJIA based on clinical evidence and expert opinion
• None carry a specific FDA indication for this particular complication

Important Considerations

• HLH/MAS is a potentially life-threatening complication of Still's disease and sJIA

• Treatment decisions should be based on:

  1. Disease severity
  2. Patient-specific factors
  3. Available clinical evidence
  4. Consultation with specialists in rheumatology and/or hematology

• Off-label use of these medications for HLH/MAS may still be appropriate in many clinical scenarios despite the lack of specific FDA indication

Dosing Information

For reference, the FDA-approved dosing of tocilizumab for sJIA (though not specifically for HLH/MAS) is:

• Intravenous administration:

  • Patients <30 kg: 12 mg/kg every 2 weeks
  • Patients ≥30 kg: 8 mg/kg every 2 weeks

• Subcutaneous administration:

  • Patients <30 kg: 162 mg every 2 weeks
  • Patients ≥30 kg: 162 mg every week